Genetic variants of microsomal metabolism and susceptibility to hydrocarbon-associated glomerulonephritis.
Hydrocarbon (HC) exposure can play a role in the development of chronic glomerulonephritis (GN). Interindividual variations in various metabolizing enzymes may influence HC biotransformation, and hence susceptibility to HC-associated GN. We evaluated the role of human genotypic polymorphism in HC-associated GN, in 41 patients (30 male, 11 female) with primary GN (17 diffuse mesangial proliferative GN, 12 focal segmental GN, 11 membranous GN, one membranoproliferative GN) and 60 (46 male, 14 female) healthy controls. Genotypic polymorphisms of (CYP) P450 2D6 (CYP2D6), glutathione S-transferases mu (GSTM1) and theta (GSTT1) and N-acetyltransferase (NAT-2) were determined using polymerase chain reaction analysis of white-blood-cell DNA. HC exposure scores were determined using a validated questionnaire, and were significantly elevated in GN patients compared to controls. While no significant differences in the various genotypic frequencies were observed in the GN group overall, compared to controls, there was a significant increase in GSTM1 null (n = 10) to GSTM1 wild type (n = 1), and NAT fast (n = 10) to slow (n = 1) acetylators, in the membranous GN group compared to controls (p < 0.05). These results suggest a possible role for GSTM1 null and NAT fast acetylator in the development of HC-associated membranous GN.
Pai
P
P
Regional Renal Unit, Royal Liverpool University Hospital, Liverpool, UK.
Hindell
P
P
Stevenson
A
A
Mason
H
H
Bell
G M
GM
D000123:Acetyltransferases / Q000235:genetics; D016009:Chi-Square Distribution; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000235:genetics*; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006838:Hydrocarbons / Q000009:adverse effects*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018709:Statistics, Nonparametric
D006838:Hydrocarbons; D019389:Cytochrome P-450 CYP2D6; D000123:Acetyltransferases; D005982:Glutathione Transferase